Nucleophiles common, table

Acceptor-substituted haloarenes have been successfully used to O-arylate phenols by aromatic nucleophilic substitution (Table 7.14). The most common arylating agents are 2-fluoro-l-nitroarenes, 2-halopyridines, 2-halopyrimidines, and 2-halotriazines. When sufficiently reactive haloarenes are used, the reaction proceeds smoothly with either the arylating agent or the phenol linked to the support. The thallium(III) nitrate catalyzed arylation of phenols with aryl iodides has been used for macrocycli-zations on solid phase [184], Burgess and co-workers have developed a solid-phase synthesis of 3-turri mimetics based on ring-closure by aromatic nucleophilic substitution (Entry 4, Table 7.14 see also Table 10.5). Phenols, alkylamines, and thiols have been successfully used as nucleophiles for this type of macrocyclization [185],... 

Nucleophiles are reactive species that seek an electron-poor center. They have an atom with a negative or partial negative charge, and this atom is referred to as the nucleophilic atom. Reacting species that have an electron-poor center are called electrophiles. These electron-poor centers usually have a positive or partial positive charge, but electron-deficient species can also be neutral (radicals and carbenes, see Chapter 5). Table 1.4 lists common nucleophiles and Table 1.5 common electrophiles. 

A list of nucleophiles commonly employed in Sn reactions is given in Table 3.2, together with examples of typical reactions involving these nucleophiles. Look at this list, and check that all the nucleophiles shown are encompassed by the above definition. 

Table 3.2 Nucleophiles commonly employed in reactions and some typical examples for each...

Preparation and Properties of Organophosphines. AUphatic phosphines can be gases, volatile Hquids, or oils. Aromatic phosphines frequentiy are crystalline, although many are oils. Some physical properties are Hsted in Table 14. The most characteristic chemical properties of phosphines include their susceptabiUty to oxidation and their nucleophilicity. The most common derivatives of the phosphines include halophosphines, phosphine oxides, metal complexes of phosphines, and phosphonium salts. Phosphines are also raw materials in the preparation of derivatives, ie, derivatives of the isomers phosphinic acid, HP(OH)2, and phosphonous acid, H2P(=0)0H. 

Synthesis by oxidation remains the first choice for commercial and laboratory preparation of quinones the starting material (1) provided the generic name quinone. This simple, descriptive nomenclature has been abandoned by Chemicaly hstracts, but remains widely used (2). The systematic name for (2) is 2,5-cyclohexadiene-l,4-dione. Several examples of quinone synonyms are given in Table 1. Common names are used in this article. 1,2-Benzoquinone (3,5-cydohexadiene-l,2-dione) (3) is also prepared by oxidation, often with freshly prepared silver oxide (3). Compounds related to (3) must be prepared using mild conditions because of their great sensitivity to both electrophiles and nucleophiles (4,5). 

Table 1 lists some of the common binucleophiles utilized in heterocyclic synthesis, the numerical prefixes referring to the relative positions of the nucleophilic centers to each other. Higher order binucleophiles, e.g. 1,5-systems, come readily to mind and the above illustrative examples rapidly increase in scope when the incorporation of these structural elements into heterocyclic systems is considered. This last group offers many opportunities for ring annulations. 

Trifluoromethanesulfonate (triflate) ion is an exceptionally good leaving grov. It can be used for nucleophilic substitution reactions on unreactive substrates. Acetolysis of cyclopropyl triflate, for example, occurs 10 times faster than acetolysis of cyclopropyl tosylate. Table 5.11 gives a conqiarison of the triftate group with some other common leaving groups. 

In this type of reaction the active drug undergoes decomposition following reaction with the solvent present. Usually the solvent is water, but sometimes the reaction may involve pharmaceutical cosolvents such as ethyl alcohol or polyethylene glycol. These solvents can act as nucleophiles, attacking the electropositive centers in drug molecules. The most common solvolysis reactions encountered in pharmaceuticals are those involving labile carbonyl compounds such as esters, lactones, and lactams (Table 1). 

Another quite common reaction involving nucleophilic attack at a carbon atom of the ring is the hydrolysis of hexahydro-oxazolo[3,4- ]pyridines and tetrahydro-oxazolo[3,4-tf]pyridin-l-ones. This reaction has been known for years and is best performed under acidic conditions, respectively, producing 2-hydroxymethyl-piperidines or pipe-colic acid derivatives in good yields representative examples are collected in Table 9. Ammoniolysis of tetrahydro-oxazolo[3,4-tf]pyridin-l -ones with amino acid derivatives has also been reported and produces substituted pipecolic acid amides in good yields <2003H(61)259>. 

The relative reactivity of a large number of nucleophiles in substitutions of the type shown in (167) has been determined (Kice et al., 1974) by measuring the rate of reaction of phenyl benzenethiolsulfonate with a variety of common nucleophiles (171) in 60% dioxan at 25°C. The results are shown in Table 8. 

TBPA + is a commonly used ET oxidant. It also possesses electrophilic reactivity, reacting with bond formation to acetate, cyanide and chloride ion, all of which have high E° values (Table 5), to give 2-substituted derivatives of [10] (Eberson and Larsson, 1986,1987). Nucleophiles with lower E° (Br-, I, ... 

The oxidation of mixtures of PBN and Nu- by TBPA + in HFP gave no spin adducts from the commonly used nucleophiles (Table 10), except in the case of triethyl phosphite and related phosphorus compounds (Eberson et al., 1996a). Thus any PBN + formed must react so slowly with Nu that the spin adduct concentration is too low to be detectable. Titration of the percentage HFP in dichloromethane which just barely allowed for the formation of the... 

Besides the addition of non-carbon nucleophiles to carbonyl and isonitrile complexes (Tables 2.2, 2.4), heteroatom-disubstituted carbene complexes can be prepared by direct addition of stable or latent carbenes to suitable complexes. The synthetic routes sketched in Figure 2.12 are those commonly used for preparing imidazoline-2-ylidene or imidazolidine-2-ylidene complexes. 

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